The invention broadly relates to container filling apparatus and is specifically directed to an improved apparatus for rapidly filling containers in a sterile environment.
Many pharmaceutical preparations produced by the pharmaceutical industry are dispensed in relatively small containers. Among these are injectable drugs and medicines which, by the nature of their use must be dispensed with a high level of sterility assurance. Elaborate techniques and apparatus are employed to maintain this high level of sterility.
To limit contamination, current container filling apparatus, which tends to be quite large, is placed in a clean room environment with the apparatus operators required to wear sterile attire, including gowns, gloves, headwear, masks and the like. The clean room itself must be maintained in a low contamination level, with conventional precautions taken as the operating personnel enter, observe and make adjustments to the equipment and leave. The apparatus itself must be periodically sterilized by steam cleaning and/or washed down with decontaminating liquid cleaners. It is difficult, time consuming and expensive to maintain the container filling apparatus and the clean room in a low level contamination.
This is particularly true with respect to the filling apparatus itself. A typical filling machine includes a number of operating stations; e.g., a container accumulator that dispenses empty (usually pre-sterilized) containers onto a lengthy container conveyor in sequential order through the use of a container transfer mechanism, a pre-fill check weigh station, a filling station which consists of a series of dispensing nozzles each of which is connected to a precision metering pump with associated control apparatus, a post-fill check weigh station, a stoppering or plugging mechanism (if required for the particular container configuration) including appropriate stopper feeder apparatus, and an eject and outfeed station that transfers the filled and sealed containers to an outfeed conveying system. Each component of the container package must be maintained in a sterile state through-out each of these operations. Conversely, the contamination of any single component may cause the finished package to become contaminated and unusable.
The primary source of contamination in a clean room environment is from individuals within the room who operate and/or monitor the filling apparatus. The air inside the room is brought in at a high rate thorough special filters that remove virtually all of the contaminants. Any liquids brought into the room such as cleaners or the drug product itself are filtered through high quality filters that again remove virtually all of the contaminants. Contamination is considered to be anything foreign to the drug product itself. This includes not only living microorganisms that are removed through filtration, steam sterilization, chemical sterilants, or other techniques, but also any particle matter that may enter the product container, including particles that carry no living organisms. An example of sources for organism free or "sterile" particles are particles of matter that enter the air when two sterile containers or two sterile machine parts rub together.
Equipment operators or other people that may enter the sterile environment contribute high levels of contaminants to the environment both in the form of microorganisms and particles. Because of this, elimination of the entry of people into the sterile zone is a significant improvement.
The subject invention is the result of an effort to produce apparatus that is less difficult as well as less costly to operate and maintain, including the ease of contamination control. Specifically, it has been found that the apparatus itself can be designed in such a way that it includes a smaller isolation or sterile zone including only those components which are directly essential to the filling and sealing process with all other components as well as equipment operators disposed outside the zone. By creating such a sterile zone and providing it with operator access ports, the need for a clean room is obviated, as is the need for the apparatus operators to be in sterile attire.
A preliminary approach to the problem was to build an isolation barrier around the upper "clean" portion of an existing filling apparatus. This resulted in a number of problems, the primary of which were inaccessibility to and extreme difficulty in cleaning and sterilizing the zone interior including the housed components, and the sealing of the components that pass from the inside to the outside of the sterilize zone.
The existing filling machine used for this preliminary approach is constructed in a manner with a large flat horizontal table top to which clean zone devices are mounted in the upward direction and to which the mechanical drive components are mounted in a downward direction from the horizontal table top. A stainless steel sheet metal cover is placed on the top side of the horizontal table top plate and serves as the division between the upper clean area and the lower mechanical space. When the concept was proposed to surround the upper clean space with an isolation barrier, several problems arose. First, the horizontal table top was relatively wide and, when surrounded by a barrier, would not allow for access to all points within the clean space with conventional techniques using glove port access. Second, since the significant amount of water and/or chemical may be used in a process to clean and/or sterilize the interior sterile zone, a simple and clean drainage system would be required. Because the conventional horizontal table top was large and flat, not allowing for good drainage, and since many mechanical devices pass through from the upper clean zone, now the sterile zone inside the isolator, to the lower mechanical space, the problems of drainage and sealing of the bottom of the sterile zone became a major problem.
In the subject invention an apparatus has been created the frame and main mounting plate of which are oriented vertically, defining sterile and non-sterile zones in side-by-side relation. Those components which are directly essential to the actual processing of the containers are disposed on one side of the plate (sterile zone) with the supporting components disposed on the opposite side (non-sterile zone). The plate, together with sterile cabinetry, encloses the essential components and defines the sterile zone. For example, the dispensing nozzles are disposed within the sterile zone, whereas the pumping devices are located within the non-sterile zone and connected to the nozzles by tubes that pass through the plate or barrier in sealed relation. The container conveyor itself, which of necessity is located in the sterile zone, also has been oriented from horizontal to vertical to significantly reduce its width. The drive means for the conveyor, however, is located in the non-sterile zone.
The result is a sterile zone that is of significantly reduced size, and an apparatus which is much more easily operated and maintained. The smaller sterile zone and the internally disposed components are easily accessed through glove ports and, since the zone is much smaller, it is easily cleaned. In addition, the absence of any mechanical devices passing through the bottom of the sterile zone enclosure allows for an extremely clean and drainable collection pan without the associated sealing problems.